Tuesday, October 28, 2014

Learning to read involves tricking the brain

In the experimental sequence, a pair of identical animals (e.g. horses) is preceded on the screen by a pair of mirror-image letters (b and d), or, in the control condition, a pair of non-mirror-image letters (f and t). 

The participant must decide in each case whether the two items (letters or animals) are identical or not. 

Credit: CNRS /Université Paris Descartes, Sorbonne-Paris-Cité /Université de Caen Basse-Normandie

While reading, children and adults alike must avoid confusing mirror-image letters (like b/d or p/q). Why is it difficult to differentiate these letters?

When learning to read, our brain must be able to inhibit the mirror-generalization process, a mechanism that facilitates the recognition of identical objects regardless of their orientation, but also prevents the brain from differentiating letters that are different but symmetrical.

A study conducted by the researchers of the Laboratoire de Psychologie du Développement et de l'Education de l'Enfant (CNRS / Université Paris Descartes / Université de Caen Basse-Normandie) is available on the website of the Psychonomic Bulletin & Review (Online First Articles).

In recent years, many studies on the process of learning to read have been based on the neuronal recycling hypothesis: the reuse of old brain mechanisms in a new adaptive role - a kind of "biological trick."

Specifically, neurons that are originally dedicated to the rapid identification of objects in the environment, through the mirror-generalization process, are "repurposed" during childhood to specialize in the visual recognition of letters and words.

In this study, the researchers showed 80 young adults pairs of images, first two letters and then two animals, asking them to determine whether they were identical.

The readers consistently spent more time determining that two animal images, when preceded by mirror-image letters, were indeed identical.

This increase in response time is called "negative priming": the readers had to inhibit the mirror-generalization process in order to distinguish letters like b/d or p/q. They then needed a little more time to reactivate this strategy when it became useful again to quickly identify animals.

Learning to read involves tricking the brain

The reader must learn to distinguish mirror-image letters (b and d) on the computer screen separated by a target fixation cross (+). 

Credit: CNRS/Université Paris Descartes, Sorbonne-Paris-Cité /Université de Caen Basse-Normandie

These results show that even adults need to inhibit the mirror-generalization process to avoid reading errors.

Children must therefore learn to inhibit this strategy when learning to read. A failure of cognitive inhibition during the recycling of visual neurons in the brain could thus be a factor in dyslexia, a direction worth exploring, in light of these findings.

More information: "The cost of blocking the mirror-generalization process in reading: Evidence for the role of inhibitory control in discriminating letters with lateral mirror-image counterparts." Grégoire Borst, Emmanuel Ahr, Margot Roell, and Olivier Houdé. Psychonomic Bulletin & Review (Online First Articles), 23 May 2014. DOI: 10.3758/s13423-014-0663-9

Learning to talk is in the genes

Researchers have found evidence that genetic factors may contribute to the development of language during infancy.

Scientists from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol worked with colleagues around the world to discover a significant link between genetic changes near the ROBO2 gene and the number of words spoken by children in the early stages of language development.

Children produce words at about 10 to 15 months of age and our range of vocabulary expands as we grow - from around 50 words at 15 to 18 months, 200 words at 18 to 30 months, 14,000 words at six-years-old and then over 50,000 words by the time we leave secondary school.

The researchers found the genetic link during the ages of 15 to 18 months when toddlers typically communicate with single words only before their linguistic skills advance to two-word combinations and more complex grammatical structures.

The results, published in Nature Communications today [16 Sept], shed further light on a specific genetic region on chromosome 3, which has been previously implicated in dyslexia and speech-related disorders.

The ROBO2 gene contains the instructions for making the ROBO2 protein. This protein directs chemicals in brain cells and other neuronal cell formations that may help infants to develop language but also to produce sounds.

The ROBO2 protein also closely interacts with other ROBO proteins that have previously been linked to problems with reading and the storage of speech sounds.

Dr Beate St Pourcain, who jointly led the research with Professor Davey Smith at the MRC Integrative Epidemiology Unit, said: "This research helps us to better understand the genetic factors which may be involved in the early language development in healthy children, particularly at a time when children speak with single words only, and strengthens the link between ROBO proteins and a variety of linguistic skills in humans."

Dr Claire Haworth, one of the lead authors, based at the University of Warwick, commented: "In this study we found that results using DNA confirm those we get from twin studies about the importance of genetic influences for language development."

"This is good news as it means that current DNA-based investigations can be used to detect most of the genetic factors that contribute to these early language skills."

The study was carried out by an international team of scientists from the EArly Genetics and Lifecourse Epidemiology Consortium (EAGLE) and involved data from over 10,000 children.

More information: 'Common Variation Near ROBO2 is Associated with Expressive Vocabulary in Infancy' by St Pourcain et al in Nature Communications.

Thursday, October 9, 2014

Rett syndrome: Autism Spectrum Disorder Mice improve with synthetic oil

When young mice with the rodent equivalent of a rare autism spectrum disorder (ASD), called Rett syndrome, were fed a diet supplemented with the synthetic oil triheptanoin, they lived longer than mice on regular diets.

Importantly, their physical and behavioral symptoms were also less severe after being on the diet, according to results of new research from The Johns Hopkins University.

Researchers involved in the study think that triheptanoin improved the functioning of mitochondria, energy factories common to all cells.

Since mitochondrial defects are seen in other ASDs, the researchers say, the experimental results offer hope that the oil could help not just people with Rett syndrome, but also patients with other, more common ASDs.

A description of the research will be published on Oct. 9 in the journal PLOS ONE.

ASDs affect an estimated one in 68 children under 8 years of age in the United States. Rett syndrome is a rare ASD caused by mutations in the MECP2 gene, which codes for methyl-CpG-binding-protein 2 (MeCP2).

Rett syndrome includes autism-like signs, such as difficulty communicating, socializing and relating to others.

Other hallmarks are seizures, decreased muscle tone, repetitive involuntary movements, and gastrointestinal and breathing problems.

These other signs are also seen in some patients with other ASDs, suggesting underlying similarities in their causes.

While the causes of most ASDs are unknown and thought to be complex, Rett syndrome is unique, and could be a source of insight for the others, because it is caused by an error in a single gene.

The research team used mice lacking the MeCP2 protein, which left them with severe Rett syndrome.

In examining those mice, what stood out, according to Gabriele Ronnett, M.D., Ph.D., who led the research project at the Johns Hopkins University School of Medicine, was that they weighed the same as healthy mice but had large fat deposits accompanied by lower amounts of nonfat tissue, such as muscle.

This suggested that calories were not being used to support normal tissue function but instead were being stored as fat.

This possibility led Ronnett and her research team to consider the role of mitochondria, which transform the building blocks of nutrients into a high-energy molecule, ATP.

This molecule drives processes such as the building of muscle and the growth of nerve cells.

Mitochondria use a series of biochemical reactions, collectively called the TCA cycle, to make this transformation possible.

According to Susan Aja, Ph.D., a research associate and lead member of the research team, "If the components of the TCA cycle are low, nutrient building blocks are not processed well to create ATP. They are instead stored as fat."

Ronnett suspected, she says, that some of Rett syndrome's neurological symptoms could stem from metabolic deficiencies caused by faulty mitochondria and reduced energy for brain cells.

"Rett syndrome becomes apparent in humans 6 to 18 months old, when the energy needs of the brain are particularly high, because a lot of new neural connections are being made," says Ronnett.

"If the mitochondria are already defective, stressed or damaged, the increased demand would be too much for them."

Previous small clinical trials in people with a different metabolic disorder suggested that dietary intervention with triheptanoin could help.

Triheptanoin is odourless, tasteless and a little thinner than olive oil. It is easily processed to produce one of the components of the TCA cycle.

When Rett syndrome mice were weaned at 4 weeks of age, they were fed a diet in which 30 percent of their calories came from triheptanoin, mixed in with their normal pelleted food.

Though far from a cure, the results of the triheptanoin treatment were impressive, the researchers say.

Treated mice had healthier mitochondria, improved motor function, increased social interest in other mice and lived four weeks, or 30 percent, longer than mice who did not receive the oil. The team also found that the diet normalized their body fat, glucose and fat metabolism.

"You can think of the mitochondria of the Rett syndrome model mice as damaged buckets with holes in them that allow TCA cycle components to leak out," says Aja.

"We haven't figured out how to plug the holes, but we can keep the buckets full by providing triheptanoin to replenish the TCA cycle."

"It is still too early to assume that this oil will work in humans with ASDs, but these results give us hope," says Ronnett.

"It's exciting to think that we might be able to improve many ASDs without having to identify each and every contributing gene."

According to Aja, additional mouse studies are needed to learn if female mice respond to the treatment, to perform a wider range of physiology and behavior tests, and, importantly, to assess the effects of triheptanoin treatment on the brain, which is considered the main driver of many Rett symptoms.

The team would also like to provide triheptanoin at earlier ages, perhaps via the mothers' milk, to mimic developmental ages at which most children are diagnosed with Rett syndrome.

Triheptanoin is currently made for research purposes only and is not available as a medicine or dietary supplement for humans.

More information: PLOS ONE: dx.plos.org/10.1371/journal.pone.0109527

Addressing Whining and unwanted behaviour in young children

Whining: That Voice!

Whining is high on the list of childhood behaviours that are really, really obnoxious to parents.

Some kids have developed this strategy into a dramatic art form, and there are a few youngsters who definitively deserve academy awards for their performances!

Many parents dread saying "No" to their kids, or not giving the children what they want, simply because of the threat of the whining that will result.

As aggravating as whining is, it can be managed. That management starts with a good understanding of where the behaviour comes from, followed by the use of a Calm, Decisive and Consistent strategy to address it.

What Causes Whining? 
You don't have to search far to discover the causes of whining. The answer to the question goes something like this.

Good parents have two sides to them, a warm, loving side and a demanding dominant side. To the child, the warm, loving part of parenting involves fun, affection and good times.

The demanding part involves learning to follow rules, acquiring skills and, basically, growing up and accepting responsibility for your actions.

The warm side of parenting is more friendly; the demanding side is more challenging.

You generally won't run into whining from your children when you are operating in the warm parenting mode.

However, you will run into whining when you are coming from the demanding side of the parenting equation.

Being demanding is a big part of your job as a parent, but it can create frustration and inappropriate reactions from your youngsters.

When you ask or demand a behaviour from a child, they have two choices: They can bite the bullet and cooperate or they can do what we call "test and manipulate."

Whining is a form of testing and manipulation.

Adults Reinforce Whining?
What makes whining work for kids?

Whining continues, and gets worse when mums, dads, grandparents or teachers do any of the following:

1. See whining as abnormal, horrible behaviour.
2. Feel angry or guilty when the kids complain.
3. Talk, argue, yell or whine back when the kids moan.
4. Or worst of all, give in to the kids and let them have their way when they whimper.

Four Useful Strategies for Parenting a Whiner 

1. Dramatically change the way you think: Whining comes from GOOD parenting; it does not mean you did something wrong.

2. Tell your child, “Whining is for your room.” Let them moan where you can’t hear it, but once they have calmed down, make sure they comply with your initial 'demand.' If they do not, then send them to their room again and repeat until they are willing to comply.

3. Use small, reasonable consequences. For example, "For every minute you whine at me, you are going to pay me 25 cents."

This 'monetary' forfeit may only work in a deeply consumer-based society where the child has a certain amount of 'disposable wealth,' like the US and the UK, but the principal of applying a 'loss' for unwanted behaviour is sound.

Keep any consequence simple, clear and short. Then no more talking, until the child changes its behaviour and complies.

There is No Negotiation and No Discussion allowed as this is simply another 'Testing' behaviour used by the child to take control of the situation and avoid doing what you want.

If you find this difficult, try avoiding eye contact with the child as well as not talking, this will help you stay stronger and stick to your goal.

4. You can also try using the age-old Counting Method from 1‐2‐3 for addressing the whining, but this should be a well understood way of correcting your child's unwanted behviour. It should be something you have practiced with your child from when they were very young.

If you want more information on correcting unwanted child behaviour and advice on sleep, bed-wetting and more serious childhood conditions, visit www.dream-angus.com

Wednesday, September 24, 2014

Children can be trained to recognise emotions

Children can using training to spot crucial cues on someone's emotional state, new research from the University of Lincoln, UK, has show.

Children can learn to better recognise other people's emotions through games which emphasise the significance of the eyes and the mouth in conveying feelings, new research has shown.

The study by cognitive neuroscientists at the University of Lincoln, UK, suggests that simple training programmes could help children better understand which expressive facial features offer the most important cues to other people's emotional state.

It is hoped the findings, published in the peer reviewed science journal PLOS ONE, could lead to new or improved interventions for children and adults who have difficulty recognising emotional states in others.

Dr Petra Pollux, a cognitive neuroscientist from the University of Lincoln's School of Psychology, said: "How we recognise and process facial expressions plays a big part in our social interaction skills."

"We've all experienced walking into a room, looking around and immediately understanding that something has happened, and that's because we're reading the expressions on people's faces."

"This ability to understand and read facial expressions is a crucial skill in development and begins at quite an early age."

"Generally, when we look at faces, we look at the eyes and the mouth, but with a definite bias towards the eyes."

"We wanted to investigate if there was a correlation between which parts of the face the children looked at and their ability to correctly pick up on the emotional state of the person in the image."

During the study nine-year-old children were shown images which conveyed varying levels of intensity of emotional expressions, from a small smile to a big grin, and asked to match it with the correct emotion. If they answered incorrectly, they were alerted by a tone.

Children and adults were not given any instructions about eye-movements, but over the four sessions learned that focusing more on the eyes offered the crucial clues they needed.

The images used in the study were digitally manipulated and showed happy, sad or fearful expressions.

An adult's ability to recognise emotions was also assessed and compared with children's, and in both cases, special eye tracking equipment was used to monitor their gaze pattern and determine which features of the face, such as the eyes, nose or mouth, they focused on most.

Children looked less often and for a shorter duration at the eyes, and more often and for longer at the mouth compared with adults.

Training for both adults and children increased the amount of time spent looking at the eyes, although for adults this was only for faces which showed a sad expression.

Children, however, showed a significant increase in the amount of time spent focused on the eyes of all three expressions after training, leading to more correct answers.

The images used in the final session were also replaced by new faces, meaning their abilities translated to different people, researchers said.

Dr Pollux added: "It's really useful to know that the way a child scans a face plays an important role in recognising emotions. This research could be used to develop mobile phone apps which turn this kind of training into a game."

Researches now hope that the findings will inform training programmes for people in need of a better understanding of recognising facial expressions, such as those with autism or other cognitive development problems.

More information: Pollux PML, Hall S, Guo K (2014) "Facial Expression Training Optimised Viewing Strategy in Children and Adults." PLOS ONE 9(8): e105418. DOI: 10.1371/journal.pone.0105418

Tuesday, September 23, 2014

Beat synchronization in preschoolers aids learning and reading skills

A team of researchers with Northwestern University in the U.S. has found that an ability to synchronize with a beat may be an indication of how well preschoolers will later do when developing reading skills.

In their paper published in Proceedings of the National Academy of Sciences, the team describes a study they undertook that involved testing for beat synchronization and sound recognition in preschoolers and what they found as a result.

Devising a test for reading aptitude prior to teaching children to read, it is believed, would help children of all levels learn better.

If a teacher knew beforehand that a child was going to have a reading disability, for example, that child could be placed into a program developed specifically for their needs, hopefully offering a better long term outcome.

Likewise, children with an exceptional aptitude for reading could be put into an accelerated program to prevent boredom.

Unfortunately, there is no such test, thus parents and teachers are left to discover a child's reading abilities on their own.

In this new effort, the researchers devised a study to find out if beat synchronicity skills might be used as the basis for such a test.

Reading specialists have suspected that there is a link between beat synchronization and both language and reading ability, reading and speech are both timing based after all.

To better understand that link the researchers arranged to test preschool volunteers.

In the first test, 35 children were given a toy drum and asked to beat it in time with an adult beating on a similar drum.

Those that could do it well were described as synchronizers, those that could not, as nonsyncronizers.

The same group of children then had electrodes pasted to their scalps to measure brain waves, as the researchers watched monitors, the children listened to sounds the researchers played, such as "da" and "ba" with no other sound, and then with background noise.

In studying the data, the researchers found that the children dubbed synchronizers in the first part of the experiment processed the played sounds with greater precision than did the nonsyncronizers.

Further tests revealed that the synchronizers did better on overall language abilities than the nonsyncronizers, which suggests that it might be possible to use the same process to test children as young as infants for later reading ability.

The researchers plan to continue monitoring the same children in the study for five years to see if their testing method is viable.

More information: Beat synchronization predicts neural speech encoding and reading readiness in preschoolers, Kali Woodruff Carr, PNAS, DOI: 10.1073/pnas.1406219111

Monday, September 22, 2014

EEG Brainwave test could improve autism diagnosis and classification



A new study by researchers at Albert Einstein College of Medicine of Yeshiva University suggests that measuring how fast the brain responds to sights and sounds could help in objectively classifying people on the autism spectrum and may help diagnose the condition earlier.

The paper was published today in the online edition of the Journal of Autism and Developmental Disabilities.

The U.S. Centers for Disease Control and Prevention estimates that 1 in 68 children has been identified with an autism spectrum disorder (ASD).

The signs and symptoms of ASD vary significantly from person to person, ranging from mild social and communication difficulties to profound cognitive impairments.

"One of the challenges in autism is that we don't know how to classify patients into subgroups or even what those subgroups might be," said study leader Sophie Molholm, Ph.D., associate professor in the Dominick P. Purpura Department of Neuroscience and the Muriel and Harold Block Faculty Scholar in Mental Illness in the department of pediatrics at Einstein.

"This has greatly limited our understanding of the disorder and how to treat it."

Autism is diagnosed based on a patient's behavioural characteristics and symptoms.

"These assessments can be highly subjective and require a tremendous amount of clinical expertise," said Dr. Molholm. "We clearly need a more objective way to diagnose and classify this disorder."

An earlier study by Dr. Molholm and colleagues suggested that brainwave electroencephalogram (EEG) recordings could potentially reveal how severely ASD individuals are affected.

That study found that children with ASD process sensory information, such as sound, touch and vision, less rapidly than typically developing children do.

The current study was intended to see whether sensory processing varies along the autism spectrum. Forty-three ASD children aged 6 to 17 were presented with either a simple auditory tone, a visual image (red circle), or a tone combined with an image, and instructed to press a button as soon as possible after hearing the tone, seeing the image or seeing and hearing the two stimuli together.

Continuous EEG recordings were made via 70 scalp electrodes to determine how fast the children's brains were processing the stimuli.

The speed with which the subjects processed auditory signals strongly correlated with the severity of their symptoms: the more time required for an ASD individual to process the auditory signals, the more severe that person's autistic symptoms.

"This finding is in line with studies showing that, in people with ASD, the microarchitecture in the brain's auditory center differs from that of typically developing children," Dr. Molholm said.

The study also found a significant though weaker correlation between the speed of processing combined audio-visual signals and ASD severity. No link was observed between visual processing and ASD severity.

"This is a first step toward developing a biomarker of autism severity, an objective way to assess someone's place on the ASD spectrum," said Dr. Molholm.

"Using EEG recordings in this way might also prove useful for objectively evaluating the effectiveness of ASD therapies."

In addition, EEG recordings might help diagnose ASD earlier. "Early diagnosis allows for earlier treatment, which we know increases the likelihood of a better outcome," said Dr. Molholm.

"But currently, fewer than 15 percent of children with ASD are diagnosed before age 4. We might be able to adapt this technology to allow for early ASD detection and therapy for a much larger percentage of children."

More information: The paper is titled "Neurophysiological Indices of Atypical Auditory Processing and Multisensory Integration are Associated with Symptom Severity in Autism."

Saturday, September 20, 2014

US Congressional Committee Hearing on the Science of Dyslexia

In an age of gridlock and choking polarization, the yesterday’s Congressional Committee Hearing on the Science of Dyslexia evoked the best qualities of US governmental process: bringing elected officials to the table with ordinary citizens in non-partisan dialogue to solve a major societal problem.

For a two hours in Rayburn room 2318 on Capitol Hill, there were no Democrats or Republicans, just people concerned about the prevalence of dyslexia in our nation’s children and the fact that millions of families are struggling, and convinced that something huge needs to be done to help these kids read, learn and thrive.

What made the event most remarkable was its emotional richness. As data points from the vast body of dyslexia science were shared by leading experts, tears flowed and laughter filled the air.

At one point, Committee Chairman Lamar Smith of Texas commented that he’d never heard such eruptions of applause and enthusiasm in a Congressional Hearing.

Best of all, the event was made accessible for everyone: its live webcast was recorded and archived; and all of the testimony was transcribed.

Here are several highlights.

Clicking on the speakers’ names will bring up a full transcript of their remarks:

Rep. Bill Cassidy of Louisiana gave some of the day’s most compelling and heart-wrenching testimony, pausing several times to wipe away tears and collect himself.

“A couple of years ago, my youngest daughter was diagnosed with dyslexia. Prompted by concerns about my daughter and my constituents’ children, I set out to learn as much as I could about dyslexia and was amazed at how much is known and yet, far too often, not incorporated into public policy and education. . ."

"If dyslexia is identified in elementary school and the appropriate resources are given to these children, America can produce more teachers, more scientists and more entrepreneurs.”

Brownley1Rep. Julia Brownley of California also shared personal perspectives as a parent.

“When my daughter Hannah struggled to learn to read, like any parent I was completely panicked about what to do next."

"It was Hannah’s dyslexia, and learning to navigate the school system, where I witnessed the good, the bad, and the ugly, that led me to public service. . ."

"This spring, Hannah received her Master’s degree in International Studies, and is now overseas saving the world with a NGO in Kenya, Africa."

"She speaks three languages, and she still misspells in all of them! I could not be prouder of her. But for every success story like Hannah, there are countless others who do not succeed.”

Sally1Dr. Sally Shaywitz of the Yale Center for Dyslexia and Creativity made a passionate plea to policy makers that now is the time to translate science into action.

“In dyslexia, remarkably in America, in the year 2014, we have not a knowledge gap but an action gap."

"We have the knowledge but it is not being put into policy and practice and far too many children and adults, too, are suffering needlessly."

"There is an epidemic of reading failure that we have the scientific evidence to treat effectively and we are not acknowledging or implementing it. . ."

"I cannot look into the face of one more child who has lost faith in himself and the world, I cannot look into the face of a child’s father who is desperately trying to hold back tears; I cannot hear once again about how a school told a mother, ‘we do not believe in dyslexia.’. . ."

"It is our hope that hearing the depth and extent of the scientific knowledge of dyslexia will alert policy makers to act and to act with a sense of urgency. ”

Max Brooks, an accomplished author and screenwriter, electrified Committee members and the gallery crowd with his personal account of living with dyslexia:

“For me, dyslexia was nearly as bad as the feelings of anxiety, shame, and low self-esteem that it caused."

"For me, ‘learned dependency’ was the real enemy, the self-narrative that ‘I can’t do this’ that can destroy children’s learning potential for the rest of their lives."

"That was ALMOST me. I’ve spent the last 30 years unlearning the lesson that dyslexia taught me, that society has no use for me. . ."

“A little awareness and flexible teaching methods could unlock unlimited potential in these kids who now think they’re losers."

"If we already have mandatory racial sensitivity training for our police, why not have mandatory dyslexia recognition training for our teachers?"

"It’s so simple, so easy, and when you look at all the other government programs designed to help citizens help themselves, it’s probably the least expensive.”

Persusasive testimony was also given by panelists Stacy Antie, a mother and parent advocate; Paul Eden, president of Landmark College; and Guinevere Eden, Director of the Center for the Study of Learning (CSL) and Professor, Department of Pediatrics, Georgetown University Medical Center.

Later on in a Q&A session with Committee lawmakers, Max Brooks revived his comment about making dyslexia training “a mandatory part of every teacher’s certificate,” instantly sparking whoops of applause from the gallery crowd, including many members of the Decoding Dyslexia movement.

And those Decoding Dyslexia members, from states as nearby as Virginia, New Jersey and Pennsylvania, and from as far away as Texas, graciously gathered for a photo op of their own before the day’s proceedings concluded.

After the Committee Hearing, attendeees and panelists enjoyed a great luncheon hosted by the National Center for Learning Disabilities, featuring a preview look at the new Understood.org initiative and a website that will launch later this month.

This was followed by speeches by an assortment of guests, including Hal Malchow, President of the International Dyslexia Association, Robbi Cooper of Decoding Dyslexia Texas, and Kristin Kane of Decoding Dyslexia Virginia.

What will be the net impact of a day like this on our nation’s dyslexic children and the parents and teachers who support them?

It’s hard to say, but there was enough knowledge, passion and experience gathered there on Capitol Hill to move mountains.

With so many diverse players assembled at the table, it brought to life the vivid slogan Learning Ally has embraced this year: Together It’s Possible.

All credit goes to Learning Ally for the content of this article.

Friday, September 12, 2014

ADHD: Medication plus parent training may help kids with aggression

Combining two medications with parent training appears to improve anger, irritability and violent tendencies in children whose attention-deficit/hyperactivity disorder (ADHD) is coupled with severe aggression, a new study suggests.

"Augmented" therapy that consists of stimulant and antipsychotic drugs, along with parent training in behavioural management techniques, was rated more effective by parents than "basic" therapy pairing only the stimulant and parent training, researchers found.

"An important finding of this study was that at the end of nine weeks, approximately half of all children receiving basic therapy were still rated by their parents as being impaired... with symptoms interfering with school or social functioning," said study author Kenneth Gadow, a professor of psychiatry at Stony Brook University in New York.

"In the augmented group receiving three interventions for aggression, about one-quarter still, at the end of nine weeks, were rated by their parents as being impaired, and that suggests, even with highly effective therapies, that many of these children still have unmet treatment needs" " he added.

The drugs used in the study, published in the September issue of the Journal of the American Academy of Child and Adolescent Psychiatry, included the widely prescribed ADHD stimulant Concerta (methylphenidate) and the antipsychotic Risperdal (risperidone).

Approximately 11 percent of American children aged 4 to 17 have been diagnosed with ADHD, which includes symptoms such as impulsivity, hyperactivity, and difficulty focusing and controlling behavior, according to the U.S. Centers for Disease Control and Prevention.

As many as half of children with ADHD also display significant, disruptive aggression, according to an editorial accompanying the new research.

"This is very common among kids with ADHD, but unfortunately it complicates the picture for treatment," said Erin Schoenfelder, a clinical psychologist at Seattle Children's Hospital and assistant professor of psychiatry and behavioural health at University of Washington.

"It really is staggeringly high."

In the new research, Gadow and his colleagues divided a group of nearly 170 children aged 6 to 12 with ADHD and aggression problems into two treatment groups, basic and augmented.

The basic group received Concerta and their parents underwent behavioral management training.

The augmented group received Concerta and parental training as well, but also took the antipsychotic Risperdal. Both groups were followed for nine weeks.

While both groups of children displayed marked reduction in symptoms, improvement ratings varied depending on whether parents or teachers were making the assessment.

Parents reported that children on augmented therapy were less likely to be impaired socially or academically by their anger and irritability than children on basic therapy.

On the other hand, teachers found few differences in these measures.

Instead, teachers of those on augmented therapy reported significant drops in ADHD symptoms, especially impulsiveness, compared with teachers of children on basic therapy.

Gadow and Schoenfelder agreed that the conflicting parent-teacher ratings demonstrate a familiar concept: that children's behaviours vary in different settings, whether or not they have ADHD.

"Just like adults, they adapt their behaviours to be more appropriate for the setting they're in," Gadow said.

"People do differ, however, in their ability to modify their behaviour from one setting to the next, and some children are much more variable [in this regard]."

Schoenfelder said long-term evidence is needed indicating that combining Concerta and Risperdal is safe in children, but "it appears from this study that the combination was well-tolerated and something practitioners could [adjust the dosage of] effectively."

"Folks trying this type of treatment should have close monitoring," she added. "This is a starting point. It's a combination doctors may try when they see this blend of aggressive and hyperactive behaviours. It certainly will require adjustment . . . but it's exciting to find something helpful for a significant proportion of the kids studied."

The study authors pointed out that their findings only apply to children with ADHD who exhibit severe irritability and peer aggression.

They noted that the study's findings are not an indication of the ADHD population as a whole.

More Information: "Risperidone Added to Parent Training and Stimulant Medication: Effects on Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct Disorder, and Peer Aggression" http://www.jaacap.com/article/S0890-8567(14)00369-4/abstract

Thursday, August 21, 2014

Children with autism have extra synapses in brain

In a study of brains from children with autism, researchers found that autistic brains did not undergo normal pruning during childhood and adolescence. 

The images show representative neurons from autistic (left) and control (right) brains; the spines on the neurons indicate the location of synapses.

Credit: Guomei Tang, PhD and Mark S. Sonders, PhD/Columbia University Medical Center

Children and adolescents with autism have a surplus of synapses in the brain, and this excess is due to a slowdown in a normal brain "pruning" process during development, according to a study by neuroscientists at Columbia University Medical Center (CUMC).

Because synapses are the points where neurons connect and communicate with each other, the excessive synapses may have profound effects on how the brain functions.

The study was published in the August 21 online issue of the journal Neuron.

A drug that restores normal synaptic pruning can improve autistic-like behaviors in mice, the researchers found, even when the drug is given after the behaviours have appeared.

"This is an important finding that could lead to a novel and much-needed therapeutic strategy for autism," said Jeffrey Lieberman, MD, Lawrence C. Kolb Professor and Chair of Psychiatry at CUMC and director of New York State Psychiatric Institute, who was not involved in the study.

Although the drug, rapamycin, has side effects that may preclude its use in people with autism, "the fact that we can see changes in behaviour suggests that autism may still be treatable after a child is diagnosed, if we can find a better drug," said the study's senior investigator, David Sulzer, PhD, professor of neurobiology in the Departments of Psychiatry, Neurology, and Pharmacology at CUMC.

David Sulzer
During normal brain development, a burst of synapse formation occurs in infancy, particularly in the cortex, a region involved in autistic behaviours; pruning eliminates about half of these cortical synapses by late adolescence.

Synapses are known to be affected by many genes linked to autism, and some researchers have hypothesized that people with autism may have more synapses.

To test this hypothesis, co-author Guomei Tang, PhD, assistant professor of neurology at CUMC, examined brains from children with autism who had died from other causes.

Thirteen brains came from children ages two to 9, and thirteen brains came from children ages 13 to 20. Twenty-two brains from children without autism were also examined for comparison.

Dr. Tang measured synapse density in a small section of tissue in each brain by counting the number of tiny spines that branch from these cortical neurons; each spine connects with another neuron via a synapse.

By late childhood, she found, spine density had dropped by about half in the control brains, but by only 16 percent in the brains from autism patients.

"It's the first time that anyone has looked for, and seen, a lack of pruning during development of children with autism," Dr. Sulzer said, "although lower numbers of synapses in some brain areas have been detected in brains from older patients and in mice with autistic-like behaviours."


Clues to what caused the pruning defect were also found in the patients' brains; the autistic children's brain cells were filled with old and damaged parts and were very deficient in a degradation pathway known as "autophagy."

Cells use autophagy (a term from the Greek for self-eating) to degrade their own components. Using mouse models of autism, the researchers traced the pruning defect to a protein called mTOR.

When mTOR is overactive, they found, brain cells lose much of their "self-eating" ability and without this ability, the brains of the mice were pruned poorly and contained excess synapses.

"While people usually think of learning as requiring formation of new synapses, "Dr. Sulzer says, "the removal of inappropriate synapses may be just as important."

The researchers could restore normal autophagy and synaptic pruning, and reverse autistic-like behaviors in the mice, by administering rapamycin, a drug that inhibits mTOR.

The drug was effective even when administered to the mice after they developed the behaviors, suggesting that such an approach may be used to treat patients even after the disorder has been diagnosed.

Because large amounts of overactive mTOR were also found in almost all of the brains of the autism patients, the same processes may occur in children with autism.

"What's remarkable about the findings," said Dr. Sulzer, "is that hundreds of genes have been linked to autism, but almost all of our human subjects had overactive mTOR and decreased autophagy, and all appear to have a lack of normal synaptic pruning.

This says that many, perhaps the majority, of genes may converge onto this mTOR/autophagy pathway, the same way that many tributaries all lead into the Mississippi River.

Overactive mTOR and reduced autophagy, by blocking normal synaptic pruning that may underlie learning appropriate behaviour, may be a unifying feature of autism."

Alan Packer, PhD, senior scientist at the Simons Foundation, which funded the research, said the study is an important step forward in understanding what's happening in the brains of people with autism.

"The current view is that autism is heterogeneous, with potentially hundreds of genes that can contribute."

"That's a very wide spectrum, so the goal now is to understand how those hundreds of genes cluster together into a smaller number of pathways; that will give us better clues to potential treatments," he said.

"The mTOR pathway certainly looks like one of these pathways. It is possible that screening for mTOR and autophagic activity will provide a means to diagnose some features of autism, and normalizing these pathways might help to treat synaptic dysfunction and treat the disease."

Journal Reference: 
Guomei Tang, Kathryn Gudsnuk, Sheng-Han Kuo, Marisa L. Cotrina, Gorazd Rosoklija, Alexander Sosunov, Mark S. Sonders, Ellen Kanter, Candace Castagna, Ai Yamamoto, Zhenyu Yue, Ottavio Arancio, Bradley S. Peterson, Frances Champagne, Andrew J. Dwork, James Goldman, David Sulzer. "Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits." Neuron, 2014; DOI: 10.1016/j.neuron.2014.07.040